Limits...
A compendium of canine normal tissue gene expression.

Briggs J, Paoloni M, Chen QR, Wen X, Khan J, Khanna C - PLoS ONE (2011)

Bottom Line: Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking.Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

View Article: PubMed Central - PubMed

Affiliation: Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Background: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis.

Methodology/principal findings: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.

Conclusions/significance: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

Show MeSH

Related in: MedlinePlus

Resolution of transcript assignment for canine probesets mapping to                            the SV2B gene locus.A. Principle component analysis of all 11,339 canine                            probesets with no gene identifier associated. B. Ensembl                            BLASTZ pairwise genomic alignment of human chromosome 15 (top panel) and                            canine chromosome 3 (bottom panel) centered on the 3′ region of                            the SV2B gene locus. Affymetrix human U133A probeset,                            205551_at (SV2B), and canine_2 probesets, CfaAffx.17603.1.S1_at (SV2B)                            and Cfa.11188.1.A1_at (unidentified) are aligned to their corresponding                            genomic regions. Canine EST evidence is shown in purple.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3104984&req=5

pone-0017107-g003: Resolution of transcript assignment for canine probesets mapping to the SV2B gene locus.A. Principle component analysis of all 11,339 canine probesets with no gene identifier associated. B. Ensembl BLASTZ pairwise genomic alignment of human chromosome 15 (top panel) and canine chromosome 3 (bottom panel) centered on the 3′ region of the SV2B gene locus. Affymetrix human U133A probeset, 205551_at (SV2B), and canine_2 probesets, CfaAffx.17603.1.S1_at (SV2B) and Cfa.11188.1.A1_at (unidentified) are aligned to their corresponding genomic regions. Canine EST evidence is shown in purple.

Mentions: A limitation encountered during our study was the large number of probesets for which no canine gene has been assigned (Table S1). Out of the 42,860 total probesets on the canine version 2.0 array, 11,339 (27%) have no gene symbol or gene name attributed using NetAffx™ annotations. In order to demonstrate that these unidentified probesets, alone, can provide important information regarding tissue selective gene expression we conducted principle component analysis. As shown in Fig. 3A, these probesets, without any prior filtering, were able to clearly separate sample replicates based on tissue. This was especially true for canine brain, pancreas, skeletal muscle and heart. However, it is unclear which transcripts these probesets are assessing and since many are highly expressed in a tissue selective manner it would be of interest to know this information. As a proof of concept, we developed an approach to re-map a subset of the top brain selective probesets for which no gene identifying information was available. This serves to describe a process for further annotation of canine transcripts and genes across all tissues, normal and diseased.


A compendium of canine normal tissue gene expression.

Briggs J, Paoloni M, Chen QR, Wen X, Khan J, Khanna C - PLoS ONE (2011)

Resolution of transcript assignment for canine probesets mapping to                            the SV2B gene locus.A. Principle component analysis of all 11,339 canine                            probesets with no gene identifier associated. B. Ensembl                            BLASTZ pairwise genomic alignment of human chromosome 15 (top panel) and                            canine chromosome 3 (bottom panel) centered on the 3′ region of                            the SV2B gene locus. Affymetrix human U133A probeset,                            205551_at (SV2B), and canine_2 probesets, CfaAffx.17603.1.S1_at (SV2B)                            and Cfa.11188.1.A1_at (unidentified) are aligned to their corresponding                            genomic regions. Canine EST evidence is shown in purple.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104984&req=5

pone-0017107-g003: Resolution of transcript assignment for canine probesets mapping to the SV2B gene locus.A. Principle component analysis of all 11,339 canine probesets with no gene identifier associated. B. Ensembl BLASTZ pairwise genomic alignment of human chromosome 15 (top panel) and canine chromosome 3 (bottom panel) centered on the 3′ region of the SV2B gene locus. Affymetrix human U133A probeset, 205551_at (SV2B), and canine_2 probesets, CfaAffx.17603.1.S1_at (SV2B) and Cfa.11188.1.A1_at (unidentified) are aligned to their corresponding genomic regions. Canine EST evidence is shown in purple.
Mentions: A limitation encountered during our study was the large number of probesets for which no canine gene has been assigned (Table S1). Out of the 42,860 total probesets on the canine version 2.0 array, 11,339 (27%) have no gene symbol or gene name attributed using NetAffx™ annotations. In order to demonstrate that these unidentified probesets, alone, can provide important information regarding tissue selective gene expression we conducted principle component analysis. As shown in Fig. 3A, these probesets, without any prior filtering, were able to clearly separate sample replicates based on tissue. This was especially true for canine brain, pancreas, skeletal muscle and heart. However, it is unclear which transcripts these probesets are assessing and since many are highly expressed in a tissue selective manner it would be of interest to know this information. As a proof of concept, we developed an approach to re-map a subset of the top brain selective probesets for which no gene identifying information was available. This serves to describe a process for further annotation of canine transcripts and genes across all tissues, normal and diseased.

Bottom Line: Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking.Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

View Article: PubMed Central - PubMed

Affiliation: Tumor and Metastasis Biology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT

Background: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis.

Methodology/principal findings: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species.

Conclusions/significance: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

Show MeSH
Related in: MedlinePlus